There is a consensus in the literature, and our preliminary data confirm, that MAO activity, both in platelets and brain, is significantly lower in smokers than in non-smokers or ex-smokers. It has also been shown that there is a component in tobacco smoke, other than nicotine, which inhibits MAO activity. However, the nature of the inhibition (reversible or irreversible), and the time course for recovery of MAO activity after smoking cessation, as well as the relationship of amount and duration of smoking to MAO activity, are not known. In the proposed study, smokers will be recruited from a smoking cessation program. Blood samples will be obtained on the "quit date", while subjects are still smoking, and at 7, 14 and 28 days following smoking cessation. Platelet MAO activity in these samples and in samples from non-smoking control subjects will be assayed. In this way, each smoking subject will serve as his/her own control, in addition to being compared to non-smoking control subjects. Smoking subjects will also be asked to report relapse and to return within two days to have another blood sample drawn. We will also assess binding of the selective MAO-B inhibitor, Ro 19-6327, in platelets of all subjects. Preliminary results show that Ro 19-6327 binding parallels MAO activity in smokers and non-smokers. Analysis of the data will include assessment of the time course of normalization of MAO activity, the relationship of MAO activity to CO and cotinine levels and to demographic and smoking history information, and the correlation of changes in MAO activity with changes in Ro 19-6327 binding. PROPOSED COMMERCIAL APPLICATION: The development of a sensitive and specific marker of smoking cessation and relapse, that has a relatively long half-life, would be of significant value to clinicians and other operating smoking cessation programs. If the measurement of platelet Ro 19-6327 binding proves reliable and valid, a non-radioactive assay can be developed and marketed that would provide accurate and informative results to the practitioner within a clinical setting, and that could improve motivation for smoking cessation.